About Us
Located on the ASU Downtown Phoenix campus, our lab resides in the ISTB-8 building. Here in the JKS lab, we take molecular-level approaches to achieve our goals of increasing the health span and delaying retinal degeneration. We use a combination of computational and experimental analytical, structural, multi-omics, and cellular data analysis approaches. We study both, model and non-model organisms, including humans, corals, sharks, and others. Our wide array of research areas is united by our overall goals of finding practical, actionable measures to assist with healthy aging and treatment for those dealing with certain rare diseases.
Dr. Klein-Seetharaman's Contributions to Science
With over twenty-five years of experience in research, Dr. Klein-Seetharaman has made numerous contributions to advancing scientific knowledge. The following is a selection of her contributions:
Protein-ligand interactions and folding
- Discovered the existence of residual structure in unfolded states of the soluble protein lysozyme (cited over 400 times) [1].
- In extension to membrane protein folding, the JKS group predicted (cited 98 times) [2] and, more recently observed experimentally [3], for the first time such a residual structure in rhodopsin, with relevance for understanding misfolding diseases [4].
GPCR Structure, Dynamics, and Allostery
- Rhodopsin is crucial in the vitally important pharmaceutical family of G protein coupled receptors, GPCRs. Dr. Klein-Seetharaman derived the most detailed insight into the structure of rhodopsin before it was crystallized in 2000, and since its crystallization, into its dynamics [5].
- Developed a strategy for introducing minimally sized 19F labels to enable NMR studies with experimentally challenging membrane proteins in general [6], a strategy which is still in use today (Liu et al., Science 335, 1106-1110, 2012). These NMR studies with rhodopsin (using 19F and 15N isotope labelling) were the first high-resolution solution NMR studies of any G protein-coupled receptor.
- Identified the first allosteric ligands for rhodopsin (anthocyanins and chlorin) and provided an in-depth description of their role in the structural perturbation of rhodopsin [7].
- The JKS group also provided a mechanistic explanation for allosteric regulation of class C GPCRs (metabotropic glutamate receptors) [8].
Protein Lipid Interactions
- Implementing a broad range of computational techniques and biophysical studies (primarily NMR spectroscopy), we have gained a highly detailed understanding of the requirements of cardiolipin interactions with proteins with practical applications in nanotechnology [9] and cell biology [10, 11].
- In a recent survey of structures of cardiolipin binding proteins, we discovered a critical role for dynamics in binding, in addition to confirming the conventional electrostatic and hydrophobic interactions [12].
Classification Techniques for Protein-Protein Interaction Prediction
- The JKS group pioneered the use of classification techniques to integrate diverse data for protein-protein interaction prediction [13], in yeast, then in humans. We are the only group world-wide that has predicted a membrane receptor interactome [14].
- We extended application of these methods to host-pathogen interactions, from HIV to Salmonella and other bacteria and viruses [15].
- Recently, we have become interested in integrating expert opinions for PPI prediction [16].
Insulin signaling and obesity
- We have shown proof of concept of using insulin as a molecular motivator for weight loss interventions [17]. This can be used to guide different diet regimens.
- For a diet based on lemon juice, we have linked the molecular motivator concept to mechanistic studies of the mechanisms of enhancing insulin sensitivity. Lemon juice also affects differentiation into mature adipocytes, characterized by large lipid droplets [18].
- The JKS group was also the first to create a coarse grained computational model of lipid droplets [19].
- In a recent survey of allosteric activators of insulin receptors, we identified a tannin which is also a component of lemon juice [20].
- In a recent, not yet published, screen of more than 400,000 docking experiments at the ASU supercomputing center, we have found several extremely potent protein-binding small molecules, providing a molecular basis for the suspected “detox” effect of lemon juice.
Support Our Lab
Donate to our research projects today to contribute to our pathbreaking research towards fighting blindness and increasing the healthspan. Your gracious financial support helps us, and in turn YOU, make a difference in the world by examining Rhodopsin and Usher's Syndrome when fighting blindness and studying humans, corals, and sharks on the metabolic level to increase the organismal health.
Donate through the ASU Foundation for a New American University website today:
Citations
For a complete list of the papers cited in this page, see here.
For a complete list of Dr. Klein-Seetharaman's published works, visit https://www.ncbi.nlm.nih.gov/pubmed/?term=klein-seetharaman.
Get in touch at jkleinse@asu.edu